The objectives of this program are: (1) To explore genetic mechanisms involved in the regulation of the malignant cell phenotype by producing cell hybrids between nonmalignant human and tumorigenic human and rodent cells and then determine if specific human chromosomes of the former can suppress the tumorigenic potential of the latter. Also, to explore in these hybrids the association of various cell phenotypes which are believed to be related to the malignant one to determine which if any of these phenotypes are significantly related to the expression of tumorigenicity. (2) To learn more about mechanisms of gene regulation in mammalian cells by fusing cells of mice carrying a defect for the regulation of a specific enzyme with rat cells which are normal in this respect and then determining if the rat chromosomes will provide the regulatory information for the expression of the mouse structural gene product. (3) To develop additional methods for transfering small amounts of genetic information from normal cells to cells deficient for specific enzymes, then regulating the activity of the transferred gene in yet another attempt at obtaining information on the gene regulatory mechanisms operating in mammalian cells.